Ruthenium-optically active phosphine complex

ABSTRACT

A ruthenium-optically active phosphine complex having, as a ligand, BICHEP which means 2,2&#39;-bis(dicyclohexylphosphino)-6,6&#39;-dimethyl-1,1&#39;-biphenyl represented by formula (I): ##STR1## is disclosed, which can catalyze asymmetric syntheses, such as asymmetric hydrogenation, asymmetric isomerization, and asymmetric silylation, exhibiting excellent catalytic activity and providing high optical purity.

FIELD OF THE INVENTION

This invention relates to a ruthenium-optically active phosphine complexwhich is useful as a catalyst for various organic syntheses,particularly asymmetric hydrogenation, asymmetric isomerization, andasymmetric silylation.

BACKGROUND OF THE INVENTION

Organic synthesis reactions using metal complexes as catalysts havehitherto been utilized for many purposes. In particular, many reportshave been made regarding asymmetric catalysts useful for asymmetricsyntheses, such as asymmetric isomerization and asymmetrichydrogenation.

For example, in order to improve the performance of these catalysts,various phosphine compounds having a special structure have hithertobeen developed as disclosed, e.g., in Kaqaku Sosetsu, Vol. 32, pp.237-238, "Yuki Kinzoku Sakutai no Kagaku" (1982), edited by The ChemicalSociety of Japan and J. D. Morrison, Asymmetric Synthesis, Vol. 5,Academic Press, Inc. (1985). Among them, many complexes in which achiral tertiary phosphine compound is coordinated to a metal, e.g.,rhodium, ruthenium, and palladium, exhibit excellent performance as acatalyst for asymmetric synthesis. In particular,2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (hereinafter abbreviated as"BINAP") is one of the excellent phosphine compounds as described inJP-A-55-61937 (the term "JP-A" as used herein means an "unexaminedpublished Japanese patent application"). Further, it has also beenreported that 2,2'-bis(diphenylphosphino)-6,6'-dimethyl-1,1'-biphenyl(hereinafter abbreviated as "BIPHENP") is an effective catalystcomponent in asymmetric hydrogenation as described in JP-A-63-135397.

The most commonly employed processes for synthesizing optically activecarboxylic acids include a process comprising chemically oxidizing anaturally occurring optically active alcohol or aldehyde to obtain acorresponding carboxylic acid, a process comprising optically resolvinga racemic carboxylic acid with an optically active amine, and a processcomprising converting a racemic carboxylic acid to its ester andpartially hydrolyzing the ester with the aid of an enzyme or amicroorganism to obtain a desired carboxylic acid.

In addition, an optically active carboxylic acid can be obtained byasymmetric hydrogenation of an α,β-unsaturated carboxylic acid in thepresence of a chiral catalyst. In this case, satisfactory results may beobtained in the syntheses of some carboxylic acids but, in general, thechoice of an optically active phosphine as a component of the chiralcatalyst is of importance, and there have been developed only few chiralphosphine compounds that are applicable for general purposes.

In an attempt to develop a phosphine compound providing catalysts havingexcellent catalytic performance, the present inventors conductedextensive investigations on tertiary phosphine compounds having axialchirality. As a result, they found that2,2'-bis(dicyclohexylphosphino)-6,6'-dimethyl-1,1'-biphenyl (hereinafterreferred to as "BICHEP") represented by formula (I): ##STR2##significantly increases stereoselectivity in asymmetric synthesis, i.e.,optical yield, as reported in Miyashita, et al., The 58th SpringtimeAnnual Meeting of The Chemical Society of Japan, Lecture Preprint II,pp. 1492 (1989).

SUMMARY OF THE INVENTION

An object of this invention is to provide a rutheniumoptically activephosphine complex having BICHEP as a ligand, which is useful as acatalyst having markedly improve catalytic activity in selectivity,durability, and the like irrespective of the reaction mode and thereaction substrate.

DETAILED DESCRIPTION OF THE INVENTION

BICHEP which is used as a ligand of the complex of the present inventioncan be synthesized by, e.g., the process reported in Miyashita, et al.,The 58th Springtime Annual Meeting of The Chemical Society of Japan,Lecture Preprint II, pp. 1492 (1989).

More specifically, o-toluidine (2) is treated with acetic anhydride toacetylate the amino grou to obtain N-acetyl-o-toluidine (3). Thecompound (3) is nitrated with nitric acid to obtain2-acetylamino-3-nitrotoluene (4) which is then hydrolyzed with ahydrochloric acid aqueous solution to obtain 2-amino-3-nitrotoluene (5).The compound (5) is diazotized with sodium nitrite in the presence ofsulfuric acid and then treated with an aqueous potassium iodide toobtain crude 2-iodo-3-nitrotoluene (6). The crude product isrecrystallized from ethanol to obtain a pale yellow pure compound (6)The compound (6) is allowed to react with stirring at 200° C. for 10hours in the presence of a copper powder, and the reaction mixture isextracted with benzene using a Soxhlet extractor to obtain6,6'-dimethyl-2,2'-dinitro-1,1'-biphenyl (7). The compound (7) ishydrogenated in the presence of a Raney nickel W2 type catalyst usinghydrazine hydrate as a hydrogen source to obtain crude6,6'-dimethyl-2,2'-diamino-1,1'-biphenyl (8). After the catalyst isremoved, the solvent is removed under reduced pressure to obtain a paleyellow pure compound (8). Subsequently, the compound (8) is dissolved ina 47% hydrobromic acid aqueous solution, and a sodium nitrite aqueoussolution is slowly added dropwise thereto under ice-cooling (0° C.),followed by stirring at -5° to -3° C. for 2.5 hours. The resultingsolution is added slowly to a separately prepared refluxing solution ofcuprous bromide in a 47% hydrobromic acid aqueous solution. After theaddition, the mixture is further heated at reflux for 2.5 hours. To thereaction mixture are added methylene chloride and water, the mixture isstirred, and an organic layer is concentrated to obtain a black crudecrystal. The crystal is purified twice by means of column chromatographyto obtain 6,6'-dimethyl-2,2'-dibromo-1,1'-biphenyl (9) as a whitecrystal. The compound (9) is dissolved in tetrahydrofuran, the solutionis cooled to -78° C., and a hexane solution of t-butyllithium is slowlyadded dropwise to the cooled solution. After the addition, thetemperature is elevated to - 45° C., and the reaction is continued foran additional 4 hours. After again cooling to -78° C., a tetrahydrofuransolution of dicyclohexylphosphinic chloride (10) is added to thereaction mixture, followed by allowing to warm to room temperature byspontaneous temperature elevation. The resulting mixture is heated atreflux for 3 hours. The solvent is removed by distillation under reducedpressure, toluene is added to the residue, and the residue is washedsuccessively with a 2N sodium hydroxide aqueous solution and water,followed by concentration. Recrystallization of the concentrate fromacetone gives racemic2,2'-bis(dicyclohexylphosphinyl)-6,6'-dimethyl-1,1'-biphenyl (11) as awhite crystal. The racemic compound (11) is dissolved in a mixed solventof ethyl acetate and chloroform under heating, and a hot ethyl acetatesolution of (-)-dibenzoyltartaric acid is added thereto, followed byallowing to stand to precipitate. The precipitated crystal is repeatedlyrecrystallized until the crystal shows a constant optical rotation

The purified crYstal is suspended in toluene, and a 2N sodium hydroxideaqueous solution is added thereto to convert the compound to a freediphosphine oxide (12). Recrystallization from chloroform-ethyl acetategives pure 2,2'-bis(dicyclohexylphosphinyl)-6,6'-dimethyl-1,1'-biphenyl(12).

Xylene and triethylamine are added to the optically pure2,2'-bis(dicyclohexylphosphinyl)-6,6'-dimethyl-1,1'biphenyl (12)([α]_(D) ²⁰ :-75.3° ), and trichlorosilane is added thereto underice-cooling. The mixture is heated at 120° C. for 2 hours and then at130° C. for 2 hours, followed by cooling to room temperature. A 30%sodium hydroxide aqueous solution is added thereto to completelydissolve any solid matter, methylene chloride is added, and the mixtureis refluxed at 60° C. for 2 hours. An organic layer is separated anddried, and the solvent is removed by distillation. The residue isrecrystallized from methanol to obtain a white crystal of BICHEP.

The ruthenium-optically active phosphine complex of the presentinvention is a ruthenium complex having BICHEP as a ligand and isrepresented by either one of the following formulae (II), (III), or(IV):

    [Ru(BICHEP)](OCOR.sup.0).sub.2                             (II)

wherein R⁰ represents a lower alkyl group (preferably containing from 1to 4 carbon atoms) or a substituted or unsubstituted aryl group (e.g., aphenyl group),

    [RuXA(BICHEP)]X'                                           (III)

wherein X and X' simultaneously represent the same halogen atom (e.g.,an idodine atom, a chlorine atom, a bromine atom); and A represents asubstituted or unsubstituted phenyl group, or

    [Ru.sub.2 Cl.sub.4 (BICHEP).sub.2 ]R.sup.00                (IV)

wherein R⁰⁰ represents a tertiary amine (preferably having lower alkylgroups each containing from 1 to 4 carbon atoms).

The complex of formula (II) can be prepared according to the processdisclosed in U.S. Pat. No. 4,739,084; the complex of formula (III) canbe prepared according to the process disclosed in European Patent366,390A; and the complex of formula (IV) can be prepared according tothe process disclosed in U.S. Pat. No. 4,691,037, respectively.

Specific but non-limitative examples of the rutheniumoptically activephosphine complex of the present invention are enumerated below.

    ______________________________________                                        [Ru(BICHEP)](OAc).sub.2                                                                          (wherein Ac means an acetyl                                                   group)                                                     [Ru(BICHEP)(p-cymene)I]I                                                      [Ru(BICHEP)(p-cymene)Cl]Cl                                                    [Ru.sub.2 Cl.sub.4 (BICHEP).sub.2 ]NEt.sub.3                                                     (wherein Et means an ethyl                                                    group)                                                     ______________________________________                                    

Among them are preferred [Ru(BICHEP)](OAc)₂ and[Ru(BICHEP)(p-cymene)I]I.

By using as a catalyst the complex according to the present invention,an optically active carboxylic acid or an ester thereof represented byformula (V): ##STR3## wherein R represents a hydrogen atom or a loweralkyl group (preferably containing from 1 to 4 carbon atoms); R¹represents a lower alkyl group (preferably containing from 1 to 4 carbonatoms), CH₂ COOR³ (wherein R³ represents a hydrogen atom or a loweralkyl group (preferably containing from 1 to 4 carbon atoms)), or NHR⁴(wherein R⁴ represents a formyl group, an acetyl group, a benzoyl group,or a chloroacetyl group); and R² represents a hydrogen atom, a loweralkyl group (preferably containing from 1 to 4 carbon atoms), or aphenyl group, can be produced.

In more detail, an α,β-unsaturated carboxylic acid represented byformula (VI): ##STR4## wherein R, R¹, and R² are as defined above, theabove-described complex catalyst, and a solvent are charged in apressure reaction vessel under a nitrogen atmosphere, and hydrogen isfilled therein to commence a hydrogenation reaction.

The catalyst of the present invention is used in an amount of from 0.02to 0.0001 mole, preferably from 0.01 to 0.001 mole, per mole of theα,β-unsaturated carboxylic acid.

Generally employed solvents can be used. Examples of suitable solventsare alcohols (e.g., methanol, ethanol, and isopropanol),tetrahydrofuran, benzene, toluene, etc., and mixtures thereof. Thesolvent is used in an amount of from 0.5 to 20 l per mole of theα,β-unsaturated carboxylic acid.

The hydrogen pressure for reaction usually ranges from 1 to 100 kg/cm²The reaction temperature is from 5° to 70° C., and preferably from 10°to 30° C. The reaction is continued until the pressure is diminished toa prescribed level, and the reaction time usually ranges from 10 minutesto 20 hours, though depending on the reaction time.

After the reaction, the solvent is removed by distillation, and theresidue is neutralized. The catalyst is then removed by extraction withchloroform, carbon tetrachloride, dichloromethane, etc. The residue isagain rendered acidic with a mineral acid and then extracted withdiethyl ether, chloroform, dichloromethane, benzene, toluene, ethylacetate, etc. to obtain a desired optically active carboxylic acid or anester thereof.

The present invention is now illustrated in greater detail withreference to the following examples, but it should be understood thatthe present invention is not construed as being limited thereto. All theparts, percents, and ratios are by weight unless otherwise specified.

Analytical instruments used in these examples are shown below.

    ______________________________________                                        High-Performance Liquid Chromatography:                                       ______________________________________                                                   Hitachi L-6000 (manufactured by Hitachi,                                      Ltd.)                                                              .sup.1 H-NMR:                                                                            Model AM-400 (400 MH) (manufactured by                                        Bruker Inc.)                                                       IR:        Model IR-810 (manufactured by Nippon Bunko                                    Kogyo K.K.)                                                        Optical Rotation:                                                                        Model DIP-4 (manufactured by Nippon Bunko                                     Kogyo K.K.                                                         Melting Point:                                                                           Micro melting point measuring apparatus                                       (manufactured by Yanagimoto Seisakusho                                        K.K.)                                                              ______________________________________                                    

PREPARATION EXAMPLE 1 Synthesis of 2-Acetylamino-3-nitrotoluene (4)

In a 1 l three-necked flask equipped with a stirrer, an Allihncondenser, and a dropping funnel was charged 650 ml (6.9 mole) of aceticanhydride, and 107 g (107 ml, 1 mole) of o-toluidine (2) was slowlyadded through the dropping funnel. After the dropwise addition, thereaction mixture was cooled to 12° to 13° C., and 126 ml (2 mole) of 70%nitric acid was slowly added thereto while maintaining this temperature.As the reaction proceeded, acetotoluide was re-dissolved andreprecipitated, the solution turned dark red, and there was separated anitro compound. The solution was poured into 3 l of ice-water whilestirring.

Milky yellow 2-acetylamino-3-nitrotoluene (4) and its isomer,2-acetylamino-5-nitrotoluene, were thus precipitated, which were thencollected in a Buchner funnel. The collected precipitates were washedfour times with 500 ml of ice-water and dried by suction by means of anaspirator to obtain a mixture of 2-acetylamino-3-nitrotoluene (4) and2-acetylamino5-nitrotoluene having a melting point of 142.2° to 143° C.and an 81% yield.

PREPARATION EXAMPLE 2 Synthesis of 2-Amino-3-nitrotoluene (5)

The wet mixture of 2-acetylamino-3-nitrotoluene (4) and2-acetylamino-5-nitrotoluene as obtained in Preparation Example 1 wasplaced in a steam distillation apparatus, and 300 ml of concentratedhydrochloric acid was added thereto. Immediately on heating and boiling,the mixture was hydrolyzed. The boiling was continued until 36 l of adistillate was collected. On cooling the distillate, there was obtained2-amino-3-nitrotoluene (5) as an orange needle-like crystal having amelting point of 92.8° to 93.2° C. and a 46% yield.

PREPARATION EXAMPLE 3 Synthesis of 2-Iodo-3-nitrotoluene (6)

In a 500 ml three-necked flask was charged 110 g (0.72 mole) of2-amino-3-nitrotoluene (5) as obtained in Preparation Example 2, and 260ml of concentrated sulfuric acid was added thereto, followed by stirringat 0° C. To the solution was added 74.8 g (1.08 mole) of sodium nitriteover 45 minutes, and the solution was stirred at 0° C. for 4 hours,whereby the solution became a dark brown suspension.

The reaction mixture was poured into 3 l of ice-water, and 1 l of anaqueous 53% potassium iodide was added thereto. After stirring at 80° C.for 10 hours, the reaction mixture was treated with 100 g of sodiumhydrogensulfite. A supernatant was removed, and insoluble matters wereextracted thrice with 500 ml of dichloromethane. An organic layer wasneutralized and washed with a saturated sodium hydrogencarbonate aqueoussolution, washed with distilled water, and then dried over anhydroussodium sulfate. The solvent was removed by distillation under reducedpressure to obtain a yellowish brown crude crystal. Recrystallization ofthe crude crystal from 150 ml of 99% ethanol gave 2-iodo-3-nitrotoluene(6) as a pale yellow crystal having a melting point of 64.8° to 65.2° C.and an 84% yield (inclusive of secondary crystals recovered from thefiltrate after recrystallization).

PREPARATION EXAMPLE 4 Synthesis of6,6'-Dimethyl-2,2'-dinitro-1,1'-biphenyl (7)

In an eggplant flask having a ground-in stopper and equipped with acondenser were charged 2-iodo-3-nitrotoluene (6) as obtained inPreparation Example 3 and an equivalent weight of a copper powder, andthe contents were stirred in an oil bath at 200° C. for 10 hours. Themixture was extracted with benzene by means of a Soxhlet extractor. Thesolvent was removed from the extract by distillation under reducedpressure, and the resulting crude crystal was recrystallized from 99%ethanol to obtain 6,6'-dimethyl-2,2'-dinitro-1,1'-biphenyl (7) as ablack needle-like crystal having a melting point of 107.4° to 108.3° C.and a 73% yield.

PREPARATION EXAMPLE 5 Synthesis of6,6'-Dimethyl-2,2'-diamino-1,1'-bichenyl (8)

The atmosphere of a 500 ml eggplant flask equipped with a three-way cockat the top and an Allihn condenser was dried under reduced pressure anddisplaced with nitrogen. In the flask was charged 13.6 g (50 mmole) of6,6'-dimethyl-2,2'-dinitro-1,1'-biphenyl (7) as obtained in PreparationExample 4 and dissolved in 120 ml of warm 99% ethanol having beenpreviously displaced with nitrogen, followed by stirring. To the mixturewas added 35 ml (0.7 mole) of hydrazine hydrate having been displacedwith nitrogen. A suspension of 3 ml of a Raney nickel W2 type catalystin ethanol was slowly added thereto by means of a syringe whilemaintaining the activity. Thereafter, the mixture was heated at refluxin an oil bath until the whole of the hydrazine was consumed.

After completion of the reaction, the catalyst was removed by filtrationthrough Celite, and the solvent was removed from the filtrate bydistillation under reduced pressure to obtain6,6'-dimethyl-2,2'-diamino-1,1'-biphenyl (8) as a pale brown crystalhaving a melting point of 132.5° to 133.8° C. and a 96.3% yield.

PREPARATION EXAMPLE 6 Synthesis of6,6'-Dimethyl-2,2'-dibromo-1,1'-biphenyl (9)

In 2.8 ml (24 mmole) of 47% hydrobromic acid was dissolved 1.0 g (4.76mmole) of 6,6'-dimethyl-2,2'-diamino-1,1'-biphenyl (8) as obtained inPreparation Example 5, and the solution was cooled to 0° C. in an icebath. A solution of 655 mg of sodium nitrite in 1.2 ml of water wasslowly added to the solution over a period of 10 minutes, followed bystirring at -5° to -3° C. for 2.5 hours. The solution was slowly addedto a refluxing solution of 73.7 mg (5 mmole) of cuprous bromide in 1.5ml (13 mmole) of 47% hydrobromic acid, and the mixture was refluxed for2.5 hours. To the reaction mixture were added 30 ml of dichloromethaneand 20 ml of distilled water to thereby thoroughly extract an organiclayer. The extract was washed successively with 10 ml of a saturatedsodium hydrogencarbonate aqueous solution, 10 ml of distilled water, and10 ml of a saturated potassium nitrate aqueous solution and dried overanhydrous sodium sulfate. The solvent was removed by distillation underreduced pressure to obtain a black oily crude crystal which was thenpurified twice by means of column chromatography according to thefollowing conditions to give 6,6'-dimethyl-2,2'-dibromo-1,1'-biphenyl(9) as a white crystal having a melting point of 90.0° to 92.3° C. and a47% yield.

    ______________________________________                                        1st Time:                                                                     Column:      Silica gel (200 mesh pass) 29 g; diameter:                                    18 mm                                                            Solvent:     1:10 (by volume) mixture of benzene and                                       hexane                                                           Recovered Fraction:                                                                        50 to 210 ml                                                     TLC:         Rf = 0.87; 100% benzene                                          Crystal Appearance:                                                                        Reddish orange crystal                                           Column Recovery:                                                                           87%                                                              2nd Time:                                                                     Column:      Silica gel (200 mesh pass) 15 g; diameter:                                    18 mm                                                            Solvent:     1:20 (by volume) mixture of benzene and                                       hexane                                                           Recovered Fraction:                                                                        50 to 90 ml                                                      TLC:         Rf = 0.52; 5% benzene-hexane                                     Crystal Appearance:                                                                        White crystal                                                    Column Recovery:                                                                           58%                                                              ______________________________________                                    

Purification may be accomplished through one column chromatography bycontrolling the column volume, the solvent concentration, and the like.

Melting Point: 87° to 93° C.

¹ H--NMR (δppm; CDCl₃): 2.0 (s, --CH₃, 6H), 7.0-7.5 (m,-Ph, 6H)

MS (M/e): 338, 340, 342

PREPARATION EXAMPLE 7 Synthesis of2,2'-Bis(dicyclohexylphosphinyl)-6,6'-dimethyl-1,1'-biphenyl (11)

In a 100 ml two-necked eggplant flask equipped with a Dimroth condenserwhose atmosphere had been dried and replaced with nitrogen were charged1.00 g (2.94 mmole) of 6,6'-dimethyl-2,2'-dibromo-1,1'-biphenyl (9) asobtained in Preparation Example 6 and 10 ml of dry tetrahydrofuran,followed by stirring at room temperature to thoroughly dissolve. Theflask was cooled to a limit (-78° C.) by using solid carbondioxide-methanol, and 13 ml (22.1 mmole) of t-butyllithium was slowlyadded dropwise to the mixture at that temperature over a period of 2hours.

Thereafter, the mixture was gradually warmed and allowed to react for atleast 4 hours while maintaining the temperature at about -45° C. Themixture was again cooled to -78° C., and 5.50 g (22.2 mmole) ofdicyclohexylphosphinic chloride (10) thoroughly dissolved in 20 ml ofdry tetrahydrofuran was added dropwise thereto, followed by stirringovernight. During the stirring, the temperature was allowed to elevatewith a Dewar vessel being fixed. After the reaction was continued untilthe mixture was warmed to room temperature by spontaneous temperatureelevation, the mixture was heated at reflux for 3 hours. The solvent wasremoved by distillation under reduced pressure, and the residue wascompletely dissolved in 20 ml of toluene. A white insoluble matter thusformed was removed by filtration.

The resulting toluene solution was washed successively twice withdistilled water, thrice with a 2N sodium hydroxide aqueous solution, andonce with distilled water. An adequate amount of potassium carbonate wasadded thereto for drying. The potassium carbonate was separated byfiltration through a cotton plug, and the solvent was removed bydistillation under reduced pressure. To the residue was added about 10ml of acetone, and the solution was sufficiently stirred while lightlywarming with a drier. A thus precipitated white crystal was collected byfiltration to obtain the novel compound of the present invention,2,2'-bis(dicyclohexylphosphinyl)-6,6'-dimethyl-1,1'-biphenyl (11) and a39.3% yield.

Melting Point: 270-277° C.

¹ H--NMR (δ ppm, CCl₄): 0.8-2.2 (m, --CH₃, --Cy, 50H), 7.0-7.4 (m, --Ph,6H)

³¹ P--NMR (δ ppm, CCl₄) (external standard: H₃ PO₄): 44.4

MS (M/e): 606 (M⁺)

IR: 2940 cm⁻¹ νCH₃ 2860 cm⁻¹ νCH₂ (cyclo) 1450 cm⁻¹ νP-PH 1180 cm⁻¹ νP=O

PREPARATION EXAMPLE 8 Optical Resolution of2,2'-Bis(dicyclohexylphosphinyl-6,6'-dimethyl-1,1'-biphenyl (12)

In a 100 ml two-necked eggplant flask equipped with an Allihn condenserwas charged 692.5 mg (1.143 mmole) of racemic2,2'-bis(dicyclohexylphosphinyl)-6,6'-dimethyl-1,1'-biphenyl (11) asobtained in Preparation Example 7, and 50 ml of ethyl acetate and 2.5 mlof chloroform were added thereto, followed by heat-refluxing todissolve. The amounts of ethyl acetate and chloroform to be added wereadjusted so that the resulting solution could become substantiallyclear.

Then, 409.5 mg (1.143 mmole) of (-)-dibenzoyltartaric acid dissolved inhot ethyl acetate was charged in the flask immediately after being takenout of the oil bath. After stirring for several seconds, the solutionwas allowed to stand overnight (a crystal began to precipitate in about30 seconds), and the thus precipitated crystal was collected byfiltration.

Optical rotations of both of a sparingly soluble diastereomer (salt ofopposite signs, i.e., (+)(-)-salt) and an easily soluble diastereomer(salt of same signs, i.e., (-)(-)-salt) were measured. If the measuredoptical rotations were not appreciably different from the values shownbelow, the product was neutralized as follows to obtain an opticallyactive diphosphine oxide. The crystal was thoroughly dissolved in about40 ml of a 2N sodium hydroxide aqueous solution and about 40 ml oftoluene with stirring, followed by liquid-liquid separation. The sodiumhydroxide layer was extracted twice or thrice with about 20 ml oftoluene.

An adequate amount of potassium carbonate was added to the toluene layerfor drying. After filtration through a cotton plug, the solvent wasremoved by distillation under reduced pressure to obtain (+)- or(-)-2,2'-bis(dicyclohexylphosphinyl)-6,6'-dimethyl-1,1'-biphenyl (12).

The resulting optically active compound (12) was repeatedlyrecrystallized using ethyl acetate and chloroform until the specificrotatory power of the crystal was no more varied.

    ______________________________________                                        (+)-Isomer      [α].sub.D                                                                           +72.7°                                                     [α].sub.435                                                                         +155.0°                                    (-)-Isomer      [α].sub.D                                                                           -75.3°                                                     [α].sub.435                                                                         -155.0°                                    ______________________________________                                    

PREPARATION EXAMPLE 9 Synthesis of Optically Active2,2'-Bis(dicyclohexylphosphino)-6,6'-dimethyl-1,1'-biphenyl (BICHEP)

In a 5 ml vessel was placed 215 mg (0.355 mmole) of the (-)-enantiomerof the optically active diphosphine oxide (12) as obtained inPreparation Example 8 ([α]_(D) -75.3° ; optical purity: 98.7%), and theatmosphere was displaced with argon. Three milliliters of anhydrousxylene was added thereto as a solvent, and the mixture was heated untilalmost a half of the (-)-diphosphine oxide dissolved. During theheating, care was taken so that the liquid temperature did not exceed100° C. in order to prevent racemization by heating. The container wasthen allowed to cool to room temperature, and 0.43 ml (4.17 mmole) oftrichlorosilane was injected therein using a previously ice-cooledsyringe. A Schlenk tube containing trichlorosilane to be added had to bekept under ice-cooling. After injection, the content was sufficientlystirred and cooled in an ice bath for several minutes. Upon addition of0.52 ml (3.73 mmole) of triethylamine, the solution turned yellow andbegan to solidify. The mixture was again stirred to form a uniform gel.The gel was further allowed to react in an oil bath at 120° C. for 4hours and then at 130° C. for 2 hours. After allowing to cool to roomtemperature, several milliliters of xylene was added thereto in anitrogen atmosphere, and the content was transferred to a Schlenk's tubein a nitrogen atmosphere by using a simplified gloved box.

Five milliliters of a 30% sodium hydroxide aqueous solution having beendisplaced with nitrogen was added to the reaction mixture to dissolveall the solid products, and 5 ml of methylene chloride was further addedthereto, followed by refluxing at 60° C. for 2 hours. An upper organiclayer was separated with a syringe, and an aqueous layer was extractedtwice with 5 ml of methylene chloride. The resulting organic layer wasdried over an adequate amount of sodium sulfate, and the solvent wasremoved by distillation in vacuo.

A thus obtained crude product was passed through a short column (SiO₂,Merck Kieselgel 60; diameter: 18 mm; height: 5 cm) and eluted withbenzene to remove the unreacted diphosphine oxide (12). The eluent wasdistilled in vacuo to remove the solvent to obtain 162 mg (percentyield: 61.9%) of (-)-BICHEP as a white solid.

    [α].sub.D.sup.20 -105.9° (c=0.816, CH.sub.2 Cl.sub.2)

The thus obtained optically active BICHEP was repeatedly recrystallizedto preferentially crystallize a one-sided enantiomer to increase itsoptical purity. The recrystallization operation was repeated until thespecific rotatory power of the crystal no more changed. The specificrotatory power of the resulting crystal was taken as a specific rotatorypower of an enantiomer of BICHEP having a optical purity of 100%. Theprocedure taken here was as follows.

The (+)-enantiomer of the optically active diphosphine oxide (12)obtained by reduction was charged in a Schlenk tube equipped with astirrer in a nitrogen atmosphere. Warm ethyl acetate which had beendisplaced with nitrogen was added thereto in small portions as a solventwith stirring. At the point when all the solid matter dissolved, thestirring was ceased, and the solution was allowed to cool to roomtemperature and then cooled in a refrigerator (-3° C.) for about 30minutes, whereby a semi-transparent crystal of BICHEP was obtained. Thesolvent was removed by using a syringe in a nitrogen atmosphere, and thecrystal was distilled in vacuo to remove any residual solvent and thendried. Specific rotatory power of the resulting crystal was measuredwith a polarimeter using methylene chloride as a solvent.

On the other hand, an optically pure crystal of (-)BICHEP was obtainedin the same manner as described above.

    ]α].sub.D.sup.32 -119.5° (c=0.826, CH.sub.2 Cl.sub.2)

Accordingly, the specific rotatory power of this optically activecompound having an optical purity of 100% was found to be +119.7° or-119.7° (the decimal fraction was within the error of the polarimeter).

Properties of BICHEP

Melting Point: 178° -182° C.

¹ H--NMR (δ ppm, CCl₄): 0.8-2.2 (m, --CH₃, --Cy, 50H) 7.1-73 (m, --Ph,6H)

³¹ --NMR (δ ppm, CD₂ Cl₂, external standard: 85% H₃ PO₄): -9.67

MS: 574 (M⁺)

EXAMPLE 1 Synthesis of(2,2'-Bis(dicyclohexylphosphino)-6,6'-dimethyl-1,1-biphenyl) RutheniumDiacetate Comolex [Ru(BICHEP)](OAc)₂

In a Schlenk tube whose atmosphere had been displaced with nitrogen werecharged 94.6 mg (0.165 mmole) of BICHEP as obtained in PreparationExample 9 and 44.3 mg (0.151 mmole/Ru) of [Ru(cycloocta-1,5-diene)Cl₂]_(n), and 20 ml of toluene was added thereto. To the mixture was added22.9 mg (0.226 mmole) of triethylamine in a nitrogen atmosphere, wherebythe reaction system became a brown suspension. The suspension washeat-refluxed for 12 hours, whereby the reaction system became a deepbrown solution. The solution was filtered through Celite, and thesolvent was removed by distillation. To a greenish brown solid thusobtained was added a suspension of 66.3 mg (0.808 mmole) of sodiumacetate in t-butanol. The resulting reddish brown suspension washeat-refluxed for 16 hours, and the resulting orange suspension wasfiltered through Celite. The solvent of the resulting brown solution wasremoved by distillation. The resulting brown solid was recrystallizedfrom a mixed solvent of 0.4 ml of toluene and 1.0 ml of hexane andvacuum dried to obtain 35.3 mg (0.0444 mmole, percent yield: 29%) of ayellow crystal.

NMR Data

¹ H--NMR (δ ppm, CDCl₃): 0.25-2.85 (m, 44H, C₆ H₁₁ --), 1.68, 2.02,2.18, 2.32 (s, 12H, Me--), 6.65-7.70 (m, 6H, aromatic)

^(--C) --NMR (δ ppm, CDCl₃): 14.1-42.7 (m, Me--, C₆ H₁₁ -), 122.9-149.8(m, aromatic), 178.2, 184.0 (s, carbonyl)

³¹ P-NMR (δ ppm, CDCl₃): 61.4, 61.8 (s) (external standard: 85% H₃ PO₄)

EXAMPLE 2 Synthesis of p-Cymene(2,2'-Bis(dicyclohexylphosphino)-6,6'-dimethyl-1,1'-biphenyl) RutheniumDiiodide Complex [Ru(BICHEP)(p-cymene)I]I

In a Schlenk tube whose atmosphere had been displaced with nitrogen wascharged 315.7 mg (0.549 mmole) of BICHEP as obtained in PreparationExample 9 and dissolved in a mixed solvent of 8 ml of methylene chlorideand 5 ml of ethanol. In another Schlenk tube was charged 268.5 mg (0.274mmole) of [Ru(p-cymeme)I₂ ]₂ and, after the atmosphere was displacedwith nitrogen, dissolved in a mixed solvent of 5 ml of methylenechloride and 10 ml of ethanol to form a deep purple solution. The deeppurple solution was transferred to the above-prepared BICHEP solution bymeans of a catheter in a nitrogen atmosphere. At this time, the reactionsystem showed no appreciable change. The mixture was heat-refluxed for 4hours, and the solvent was removed by distillation. The residual solidwas recrystallized from a mixed solvent of 8 ml of methylene chlorideand 2 ml of diethyl ether and vacuum dried to obtain 328.8 mg (0.309mmole, yield: 56.3%) of a brownish purple crystal.

NMR Data

¹ H--NMR (δ ppm, CDCl₃): 0.37-2.30 (m, 44H, C₆ H₁₁ -), 1.27 (d, 6H,isopropyl-Me), 2.04, 2.10 (s, 6H, BICHEP--Me), 2.35 (s, 3H, Me), 3.00(m, 1H, CH), 3.00-3.47 (br, 4H, arene), 5.32-5.55, 7.28-7.53 (m, 6H,aromatic)

³¹ P--NMR (6 ppm, CDCl₃): 69.4, 77.8 (br) (external standard: 85% H₃PO₄)

REFERENCE EXAMPLE 1 Asymmetric Hydrogenation

In a 100 ml glass-made pressure vessel which had been purged withnitrogen were charged successively with 79.3 mg (0.1 mmole) of the[Ru((R)-BICHEP)](OAc)₂ complex as obtained in Example 1, 30 ml ofethanol, and 2.33 g (10 mmole) of ethyl (Z)-α-acetamidocinnamate. Themixture was subjected to hydrogenation at 25° C. under a hydrogenpressure of 5 kg/cm² for 5 hours. The reaction mixture was subjected tosilica gel column chromatography to remove the catalyst. The residue wasdetermined by ¹ H--NMR and optical rotation and found to be ethyl2-acetylamino-3-phenylpropionate having an optical purity of 91% ee.

REFERENCE EXAMPLE 2 Asymmetric Hydrogenation

In a 100 ml glass-made pressure vessel which had been purged withnitrogen were charged successively with 93.6 mg (0.1 mmole) of the[Ru(S)-BICHEP)(p-cymene)I]I complex as obtained in Example 2, 30 ml ofethanol, and 2.33 g (10 mmole) of ethyl (Z)-α-acetamidocinnamate. Themixture was subjected to hydrogenation at room temperature under ahydrogen pressure of 5 kg/cm² for 45 hours. The reaction mixture wastreated in the same manner as in Reference Example 1 to obtain ethyl2-acetylamino-3-phenylpropionate having an optical purity of 85% ee.

As described above, the ruthenium-optically active phosphine complexaccording to the present invention can catalyze asymmetric syntheses,such as asymmetric hydrogenation, asymmetric isomerization, andasymmetric silylation, exhibiting excellent catalytic activity andproviding high optical purity.

While the invention has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one skilled in theart that various changes and modifications can be made therein withoutdeparting from the spirit and scope thereof.

What is claimed is:
 1. A ruthenium-optically active phosphine complexhaving, as a ligand, BICHEP which means2,2'-bis(dicyclo-hexylphosphino)-6,6'-dimethyl-1,1'-biphenyl representedby formula (I): ##STR5##
 2. A ruthenium-optically active phosphinecomplex as in claim 1, represented by formula (II):

    [Ru(BICHEP)](OCOR.sup.0).sub.2                             (II)

wherein R⁰ represents a lower alkyl group or a substituted orunsubstituted aryl group.
 3. A ruthenium-optically active phosphinecomplex as in claim 1, represented by formula (III):

    [RuXA(BICHEP)]X'                                           (III)

X and X' simultaneously represent the same halogen atom; and Arepresents a substituted or unsubstituted phenyl group.
 4. Aruthenium-optically active phosphine complex as in claim 1, representedby formula (IV):

    [Ru.sub.2 Cl.sub.4 (BICHEP).sub.2 ]R.sup.00                (IV)

wherein R⁰⁰ represents a tertiary amine.
 5. A ruthenium-optically activephosphine complex as in claim 2, represented by [Ru(BICHEP)](OAc)₂,wherein Ac means an acetyl group.
 6. A ruthenium-optically activephosphine complex as in claim 3, represented by[Ru(BICHEP)(p-cymene)I]I.